BHQ-Cyanine-Based 'Off–On' Long-Circulating Assembly as a Ferroptosis Amplifier for Cancer Treatment: A Lipid-Peroxidation Burst Device
| Autor: | Renjie Luo, Yidan Bai, Feng Feng, Jun Dou, Zhang Zhongtao, Mangmang Sang, Wenyuan Liu, Fulei Liu |
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| Rok vydání: | 2019 |
| Předmět: |
Alkanesulfonates
Programmed cell death Materials science Mice Nude Breast Neoplasms 02 engineering and technology 010402 general chemistry 01 natural sciences Rats Sprague-Dawley Lipid peroxidation Mice chemistry.chemical_compound In vivo Animals Ferroptosis Humans General Materials Science Photosensitizer Magnetite Nanoparticles Inner mitochondrial membrane Mice Inbred BALB C Glutathione Sorafenib 021001 nanoscience & nanotechnology Malondialdehyde Xenograft Model Antitumor Assays Rats 0104 chemical sciences chemistry MCF-7 Cells Biophysics Female Lipid Peroxidation 0210 nano-technology Azo Compounds Iron oxide nanoparticles |
| Zdroj: | ACS Applied Materials & Interfaces. 11:42873-42884 |
| ISSN: | 1944-8252 1944-8244 |
| DOI: | 10.1021/acsami.9b12469 |
| Popis: | Ferroptosis is an iron-dependent cell death caused by accumulation of lipid peroxidation (LPO), which is a new strategy for cancer treatment. Th current ferroptosis therapy nanodevices have low efficiency and side effects generally. Hence, we developed a Black Hole Quencher (BHQ)-based fluorescence "off-on" nanophotosensitizer complex assembly (CSO-BHQ-IR780-Hex/MIONPs/Sor). CSO-connected BHQ-IR780-Hex and -loaded magnetic iron oxide nanoparticles (MIONPs) and sorafenib (Sor) formed a very concise functionalized delivery system. CSO-BHQ-IR780-Hex disassembled by GSH attack and released IR780-Hex, MIONPs, and sorafenib. IR780-Hex anchored to the mitochondrial membrane, which would contribute to amplifying the efficiency of the photosensitizer. When NIR irradiation was given to CSO-BHQ-IR780-Hex/MIONPs/Sor-treated cells, iron supply increased, the xCT/GSH/GPX-4 system was triggered, and a lot of LPO burst. A malondialdehyde test showed that LPO in complex assembly-treated cells was explosive and increased about 18-fold compared to the control. The accumulation process of particles was monitored by an IR780-Hex photosensitizer, which showed an excellent tumor target ability by magnetic of nanodevice in vivo. Interestingly, the half-life of sorafenib in a nanodevice was increased about 26-fold compared to the control group. Importantly, the complex assembly effectively inhibits tumor growth in the breast tumor mouse model. This work would provide ideas in designing nanomedicines for the ferroptosis treatment of cancer. |
| Databáze: | OpenAIRE |
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